NUS Graduate Program in Bioengineering, Centre for Life Sciences #05-01, 28 Medical Drive, Singapore 117456, Singapore.
Int J Pharm. 2010 Nov 15;400(1-2):194-200. doi: 10.1016/j.ijpharm.2010.08.026. Epub 2010 Aug 27.
Cationic nanoparticles of biodegradable polymers such as poly (lactide) (PLA) have been shown to be promising carrier systems for DNA and siRNA delivery. However, the parameters which influence the transfection efficiency have not been investigated in details. In this work, four groups of cationic PLA-based nanoparticles were synthesized by the nanoprecipitation method and solvent evaporation method with polyethyleneimine (PEI) and chitosan as two types of surface coating materials. Cationic poly (D,L-lactide-co-glycolide) (PLGA)-PEI, PLGA-chitosan and methoxy poly (ethylene glycol)-poly (lactide) (mPEG)-PLA/PEI, mPEG-PLA-chitosan nanoparticles were characterized in terms of size and size distribution by laser scattering, surface charge by zeta potential measurement, and surface chemistry by X-ray electron spectroscopy (XPS). The four type pg nanoparticles were compared for their interaction with siRNA and nanoparticles mediated siRNA transfection efficiency with a hepatitis B model, where the inhibition effects of the double strand RNA (dsRNA) mediated by the four types of nanoparticles were evaluated by measuring the HBsAg expression level. The highest inhibition effect of HBsAg (the surface antigen of the hepatitis B Virus (HBV), which indicates current hepatitis B infection) expression was achieved by the mPEG-PLA-PEI nanoparticles mediated siRNA transfection. The results demonstrated that the siRNA delivery follows a size and surface charge dependant manner.
基于聚（乳酸）（PLA）等可生物降解聚合物的阳离子纳米颗粒已被证明是 DNA 和 siRNA 递送的有前途的载体系统。然而，影响转染效率的参数尚未详细研究。在这项工作中，通过纳米沉淀法和溶剂蒸发法，用聚乙烯亚胺（PEI）和壳聚糖作为两种表面涂层材料，合成了四组阳离子 PLA 基纳米颗粒。通过激光散射对阳离子聚（D，L-丙交酯-共-乙交酯）（PLGA）-PEI、PLGA-壳聚糖和甲氧基聚（乙二醇）-聚（乳酸）（mPEG）-PLA/PEI、mPEG-PLA-壳聚糖纳米颗粒的粒径和粒径分布进行了表征，通过zeta 电位测量对表面电荷进行了表征，通过 X 射线电子能谱（XPS）对表面化学进行了表征。比较了这四种类型的 pg 纳米颗粒与 siRNA 的相互作用以及纳米颗粒介导的 siRNA 转染效率，用乙型肝炎模型评估了四种纳米颗粒介导的双链 RNA（dsRNA）的抑制效果，通过测量 HBsAg 的表达水平来评估。mPEG-PLA-PEI 纳米颗粒介导的 siRNA 转染实现了 HBsAg（乙型肝炎病毒（HBV）的表面抗原，表明当前乙型肝炎感染）表达的最高抑制效果。结果表明，siRNA 的递送遵循尺寸和表面电荷依赖性。
